We plan to study reactions of different portions of the nephron to various factors under controlled conditions in order to clarify physiologic and disease mechanisms in the kidney, to aid in understanding the pathogenesis of etiologic processes, to aid in diagnosis, and to evaluate treatment of renal disease. Light and electron microscopy will be used to correlate function and ultrastructure. Comparison with pertinent selected human renal biopsies will give orientation to the experimental animal studies. Promising leads obtained from previous investigations will be studied further. These areas will include changes in the filtering layers of the glomerular capillary wall in proteinuria, the reactions of mesangial cells and their role in controlling glomerular capillary blood flow, focal glomerulonephritis, the nephrotic syndrome, reactions of hyperplastic juxta-glomerular cells and of medullary granular cells in renovascular hypertension, and the reactions in cellular immunity of lymphoid and target cells in vitro.